We propose to continue our study of the reactions of the airborne pollutants ozone, nitrogen dioxide, and cigarette smoke. All of these toxic pollutants either are free radicals or cause the formation of free radicals when they react with organic materials. We have chosen initially to concentrate our study on the reactions of these toxic agents with polyunsaturated fatty acids (PUFA) in a series of model systems of increasing complexity, starting with simple chemical model systems such as PUFA esters and lipids, then to aqueous systems such as liposome, and finally to biological membranes, in pulmonary alveolar macrophages. We have established that both ozone and nitrogen dioxide initiate the destructive autoxidation of PUFA both in lipophilic and hydrophilic systems. The literature clearly establishes that this destructive autoxidation causes damage to membranes, occurs in vivo, and can cause cell death. It is the aim of our research to provide a continuum in understanding between the chemical events that occur when PUFA are exposed to ozone or nitrogen dioxide and the biological damage that these agents cause. We have shown that autoxidation of PUFA produces prostaglandins. This suggests that the bioorganic chemistry of endoperoxides and cyclic peroxides related to those in prostaglandin biosynthesis is of considerable importance in free radical biology. In our study of cigarette smoke, we have identified and quantified the radicals present in filtered smoke by the technique of spin traps and electron spin resonance (ESR). We are investigating the reactions of radicals in smoke with biologically important molecules. For example, we have shown that smoke radicals react with the tar produced by cigarettes; we believe that these reactions are involved in the carcinogenicity of smoke.